Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality

K. Sasai, J. M. Parant, M. E. Brandt, J. Carter, H. P. Adams, S. A. Stass, A. M. Killary, H. Katayama, S. Sen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G2-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.

Original languageEnglish
Pages (from-to)4122-4127
Number of pages6
JournalOncogene
Volume27
Issue number29
DOIs
Publication statusPublished - Jul 3 2008
Externally publishedYes

Keywords

  • Chromosome segregation
  • Cre-LoxP recombination
  • Mitotic spindle
  • Morula/blastocyst
  • Mouse Aurora kinase A (Aurka) gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Sasai, K., Parant, J. M., Brandt, M. E., Carter, J., Adams, H. P., Stass, S. A., Killary, A. M., Katayama, H., & Sen, S. (2008). Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. Oncogene, 27(29), 4122-4127. https://doi.org/10.1038/onc.2008.47